1.13.11.11: tryptophan 2,3-dioxygenase
This is an abbreviated version!
For detailed information about tryptophan 2,3-dioxygenase, go to the full flat file.
Word Map on EC 1.13.11.11
-
1.13.11.11
-
indoleamine
-
kynurenine
-
immunotherapy
-
heme
-
serotonin
-
checkpoint
-
l-trp
-
n-formylkynurenine
-
quinolinic
-
tolerogenic
-
3-monooxygenase
-
3,4-dioxygenase
-
heme-containing
-
2,3-dioxygenase-1
-
tryptophan-degrading
-
3-hydroxyanthranilate
-
indoleamine-2,3-dioxygenase
-
picolinic
-
tryptophan-catabolizing
-
pyrrolase
-
3-hydroxykynurenine
-
medicine
-
drug development
- 1.13.11.11
- indoleamine
- kynurenine
-
immunotherapy
- heme
- serotonin
-
checkpoint
- l-trp
- n-formylkynurenine
-
quinolinic
-
tolerogenic
-
3-monooxygenase
-
3,4-dioxygenase
-
heme-containing
-
2,3-dioxygenase-1
-
tryptophan-degrading
- 3-hydroxyanthranilate
- indoleamine-2,3-dioxygenase
-
picolinic
-
tryptophan-catabolizing
-
pyrrolase
- 3-hydroxykynurenine
- medicine
- drug development
Reaction
Synonyms
33737, BRAFLDRAFT_210874, C28H8.11, EC 1.11.1.4, hTDO, IDO-1, IDO-2, IDO1, IDO2, indoleamine 2,3-dioxygenase 1, indoleamine 2,3-dioxygenase 2, TDO, TDO2, TDOa, tryptophan 2,3-dioxygenase, tryptophan 2,3-dioxygenase 2, tryptophan 2,3-dioxygenase-2, tryptophan-2,3-dioxygenase, v1g157887, vCG5163, XcTDO
ECTree
Advanced search results
General Information
General Information on EC 1.13.11.11 - tryptophan 2,3-dioxygenase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
drug target
evolution
malfunction
metabolism
physiological function
additional information
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. Despite their poor sequence similarities, their active sites are highly conserved, and therefore allow the design of inhibitors with multiple activities that can target at least two isoforms
drug target
human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) are closely linked to the pathogenesis of Parkinson's disease
drug target
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs
drug target
the enzyme (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers. Therefore, TDO inhibition may be a useful therapeutic intervention for cancers
drug target
tryptophan 2,3-dioxygenase is a therapeutic target for Parkinson's disease
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
evolution
-
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
-
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
-
TDO knockout mice require a minimum of 0.06% dietary L-Trp, which value is about 2 mg/d/mouse
malfunction
alterations in the activity of tryptophan 2,3-dioxygenase cause imbalances in the levels of serotonin and other neuroactive metabolites which can contribute to motor, psychiatric, gastrointestinal, and other dysfunctions often seen in Parkinson's disease
malfunction
pharmacological inhibition or knockdown of the enzyme (TDO2) in adjuvant-induced arthritis-fibroblast-like synoviocytes results in a reduced proliferation, secretion, migration and invasion
malfunction
pharmacological inhibition or knockdown of the enzyme (TDO2) in adjuvant-induced arthritis-fibroblast-like synoviocytes results in a reduced proliferation, secretion, migration and invasion
malfunction
-
TDO knockout mice require a minimum of 0.06% dietary L-Trp, which value is about 2 mg/d/mouse
-
comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
metabolism
the first and rate limiting step of the kynurenine pathway is carried out by two heme-containing enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52), which differ in their tissue distribution and regulation
metabolism
weaning alters the tryptophan 2,3-dioxygenase activity by affecting the acetylation state of the enzyme in piglets livers
metabolism
-
comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
-
the enzyme is involved in L-tryptophan catabolism to produce bioactive metabolites including kynurenine, kynurenic acid, quinolinic acid, and the coenzyme NAD+ via the kynurenine pathway
physiological function
the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
physiological function
the human heme enzyme tryptophan 2,3-dioxygenase (hTDO) catalyzes the insertion of dioxygen into its cognate substrate, L-tryptophan (L-Trp)
physiological function
-
tryptophan 2,3-dioxygenase (TDO) has a immunomodulatory function that promotes tumoral immune resistance and proliferation
physiological function
tryptophan 2,3-dioxygenase (TDO) is one of the two key enzymes in the kynurenine pathway, it catalyzes the indole ring cleavage at the C2-C3 bond of L-tryptophan. This is a rate-limiting step in the regulation of tryptophan concentration in vivo. In addition to its role in protein synthesis, 95% of L-Trp in the human body is processed by the kynurenine pathway, leading to the production of nicotinamide adenine dinucleotide. Enzyme TDO is expressed in many tumor cells and is related to reduction of antitumor immune response
physiological function
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO)
physiological function
TDO2 is the key enzyme responsible for reduced tryptophan levels in mut-MED12 leiomyoma
physiological function
the enzyme (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine
physiological function
the enzyme catalyses the rate-limiting step in the kynurenine pathway, an important biochemical mechanism for immunological responsecancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine thr immune systems of patients, leading to poor disease outcomes
physiological function
the enzyme is overactivated or overexpressed in many human cancers, which is associated with poor patient outcomes
physiological function
the enzyme is responsible for L-tryptophan (L-Trp) homeostasis. Expression of TDO2 in cancer cells results in the inhibition of immune-mediated tumor rejection due to an enhancement of L-Trp catabolism via the kynurenine pathway
physiological function
the enzyme plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis
physiological function
the enzyme plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis
physiological function
the first step of the kynurenine pathway for L-tryptophan (L-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase
physiological function
-
the kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes - tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) - leading initially to the formation of N-formylkynurenine
physiological function
tryptophan 2,3-dioxygenase catalyzes the oxidation of the essential amino acid tryptophan to N-formylkynurenine which is rapidly converted to a series of biological active metabolites including kynurenine via the kynurenine pathway
physiological function
tryptophan 2,3-dioxygenase is a key enzyme of tryptophan metabolism at the entry of the kynurenine pathway which moderates production of neuroactive compounds primarily outside the central nervous system
physiological function
tryptophan 2,3-dioxygenase is the rate-limiting enzyme in the kynurenine pathway. It catalyzes the oxidative breakdown of the essential amino acid, L-tryptophan to N-formylkynurenine. This reaction is also carried out by an analogous hemoprotein, indoleamine 2,3-dioxygenase, albeit with a much lower substrate selectivity
physiological function
tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. A mechanism allows stable tryptophanemia despite varying levels of tryptophan supply in the diet. High tryptophan availability stabilizes tryptophan 2,3-dioxygenase in the liver, allowing efficient tryptophan catabolism. In contrast, low tryptophan levels trigger proteasome-mediated degradation of tryptophan 2,3-dioxygenase, thereby stopping tryptophan catabolism and preventing hypotryptophanemia
physiological function
-
the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
-
physiological function
-
the first step of the kynurenine pathway for L-tryptophan (L-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase
-
eight residues play critical roles in L-tryptophan oxidation, i.e. Y42, Y45, F72, H76, F140, R144, S151, and H328. hTDO must form an oligomer to exhibit activity
additional information
-
eight residues play critical roles in L-tryptophan oxidation, i.e. Y42, Y45, F72, H76, F140, R144, S151, and H328. hTDO must form an oligomer to exhibit activity
additional information
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
additional information
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
additional information
-
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
-